» Articles » PMID: 33278361

A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization

Abstract

Mre11-Rad50-Xrs2 (MRX) is a highly conserved complex with key roles in various aspects of DNA repair. Here, we report a new function for MRX in limiting transcription in budding yeast. We show that MRX interacts physically and colocalizes on chromatin with the transcriptional co-regulator Mediator. MRX restricts transcription of coding and noncoding DNA by a mechanism that does not require the nuclease activity of Mre11. MRX is required to tether transcriptionally active loci to the nuclear pore complex (NPC), and it also promotes large-scale gene-NPC interactions. Moreover, MRX-mediated chromatin anchoring to the NPC contributes to chromosome folding and helps to control gene expression. Together, these findings indicate that MRX has a role in transcription and chromosome organization that is distinct from its known function in DNA repair.

Citing Articles

Parasitic plasmids are anchored to inactive regions of eukaryotic chromosomes through a nucleosome signal.

Girard F, Even A, Thierry A, Ruault M, Meneu L, Larrous P EMBO J. 2025; .

PMID: 40016420 DOI: 10.1038/s44318-025-00389-1.


Transcription factor condensates, 3D clustering, and gene expression enhancement of the regulon.

Lee J, Simpson L, Li Y, Becker S, Zou F, Zhang X Elife. 2024; 13.

PMID: 39347738 PMC: 11441978. DOI: 10.7554/eLife.96028.


DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions.

Li Y, Lee J, Bai L Nat Commun. 2024; 15(1):4358.

PMID: 38778058 PMC: 11111806. DOI: 10.1038/s41467-024-48718-y.


Transcription Factor Condensates Mediate Clustering of Regulon and Enhancement in Gene Expression.

Lee J, Simpson L, Li Y, Becker S, Zou F, Zhang X bioRxiv. 2024; .

PMID: 38370634 PMC: 10871269. DOI: 10.1101/2024.02.06.579062.


Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.

Vertemara J, Tisi R Int J Mol Sci. 2023; 24(15).

PMID: 37569756 PMC: 10418313. DOI: 10.3390/ijms241512377.


References
1.
Soutourina J . Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol. 2017; 19(4):262-274. DOI: 10.1038/nrm.2017.115. View

2.
Tittel-Elmer M, Lengronne A, Davidson M, Bacal J, Francois P, Hohl M . Cohesin association to replication sites depends on rad50 and promotes fork restart. Mol Cell. 2012; 48(1):98-108. PMC: 3904740. DOI: 10.1016/j.molcel.2012.07.004. View

3.
DAmours D, Jackson S . The Mre11 complex: at the crossroads of dna repair and checkpoint signalling. Nat Rev Mol Cell Biol. 2002; 3(5):317-27. DOI: 10.1038/nrm805. View

4.
Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R . The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell. 2015; 162(5):1016-28. PMC: 4644235. DOI: 10.1016/j.cell.2015.07.059. View

5.
van Dijk E, Chen C, dAubenton-Carafa Y, Gourvennec S, Kwapisz M, Roche V . XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast. Nature. 2011; 475(7354):114-7. DOI: 10.1038/nature10118. View